Mesenchymal stem cells (MSCs) are self-renewing multipotent cells capable of differentiating into several cell lineages including osteoblasts, chondrocytes, and adipocytes. MSCs have successfully been isolated from bone marrow, adipose, peripheral blood, umbilical cord blood and matrix, fetal blood and liver, connective tissue of dermis, and skeletal muscle sources.
The multi-differentiation potential of MSC raises a clinical interest to employ these cells for regeneration purposes, for example, in osteogenesis imperfecta. MSCs exhibit an immunomodulatory potential and have been shown to inhibit T and NK cell proliferation in vitro. Because of their immunosuppressive, self-renewal, and multi-lineage differentiation properties, MSCs have been used in human clinical trials for treatment of graft-versus-host disease, multiple sclerosis, and spinal cord injury. Since the yields of MSCs isolated from human tissue compartments are very low (0.001% to 0.01% of recovered nucleated cells), MSCs must be expanded in vitro for therapeutic application. But in vitro expansion results in gradual loss of their immunosuppressive potential.
The lack of maintenance of the immunosuppressive capability of MSCs limits their therapeutic application. Thus, more effective strategies to maintain the immunosuppressive potential of MSCs is needed. The mechanisms underlying MSC's immunosuppressive properties are not yet fully elucidated; however, several mediators such as Human leukocyte antigen (HLA)-G, indoleamine 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2), and inducible nitric oxide synthase (iNOS) have been proposed. It has been observed that HLA-G expression in MSCs is very low and diminishes during in vitro expansion. M. Giuliani, M. Fleury, A. Vernochet, F. Ketroussi, D. Clay, B. Azzarone, J. J. Lataillade, A. Durrbach, Long-lasting inhibitory effects of fetal liver mesenchymal stem cells on T-lymphocyte proliferation, PLoS One 6 (2011) e19988.
Lack of sustained imunosuppression impacts the potential therapeutic application of MSCs in regenerative medicine and prevention of graft-versus-host disease. Thus, strategies to enhance and maintain MSC immunosuppressive effects would substantially improve their therapeutic utility